The proposed project is aimed at the development of Laser Activated Nano-Thermolysis as Cell Elimination Technology (LANTCET) for chemical-free detection and selective destruction (elimination) of tumor cells in superficial tissue layer and with single-cell selectivity thus excluding the damage to collateral normal cells. LANTCET includes four major steps: (1) topical application of non-toxic conjugates of gold nanoparticles (NP) with follow up selective formation of intracellular NP clusters due to endocytosis;(2) optical detection of tumor cells in tissue with normal cells by registering NP cluster-specific optical scattering signals, (3) selective mechanical destruction (thermolysis) of individual tumor cells by pulsed laser-induced photo-thermal intracellular micro- bubbles (PTB) selectively generated around NP clusters in target cells, and (4) real-time optical guidance of tumor cell damage by detecting (imaging) the PTB-specific scattering optical signals. The detection, destruction and optical guidance processes are completed within microseconds and with one devise. The efficacy, specificity and selectivity of the LANTCET is provided by NP cluster - PT bubble mechanism of cell optical detection and destruction that concentrates all absorbed laser energy within individual tumor cells and thus excludes thermal damage of normal cells and tissues. Optical monitoring of NP clusters and PTBs in a tissue layer will guide the ablative laser pulse to the tumor cell and help to determine optimal laser fluence for the 100% damage of tumor cells and real-time optical validation of tumor destruction. PUBLIC HEALTH RELEVANCE: Superficial cancers such as cutaneous tumors and early lesions of the mucosa of the upper aerodigestive tract are most often treated by surgical excision. However for diffuse areas of the skin or for mucosa in functionally or cosmetically important structures, surgical excision can be extremely morbid. Consequently, the development of alternative treatment strategies that more selectively target neoplastic cells could enhance outcomes for patients with these tumor types. The advent of molecularly targeted cancer therapy has shown significant promise with a recently completed trial showing a survival benefit when a monoclonal antibody that binds to the Epidermal Growth Factor Receptor (EGFR), which is highly expressed by some cancer cells, is used for the treatment of squamous cell carcinoma of the upper aerodigestive tract (SCCHN). The nearly simultaneous development of gold nanoparticles which can be optically activated in situ to generate the intracellular photothermal bubbles (PTB) suggests that coupling molecular targets of tumor cells with nanoparticles for activation of intracellular PTB could serve as an effective strategy for detecting and treating cancer at cell level.